The development of most chronic diseases is a multifactorial process involving issues of susceptibility (from genetic or nutritional factors)and environmental exposures. This project focuses on hormonally- mediated diseases that particularly impact women and minority populations. 1) Data have been collected from 110 women participating in a longitudinal study of perimenopausal bone density, to be used to determine the extent to which vitamin D receptor polymorphisms affect bone mineral density. 2) We are developing a study of the long-term effect of prenatal DES exposure on bone, involving follow-up of 200 women born in 1951-52 whose mothers participated in a randomized, controlled trial. This study will help elucidate the role of estrogens during early development on adult bone density. 3)Data analysis is continuing in a cohort study of 1000 women who participated in a prospective study of menstrual cycle patterns begun in 1935. In an analysis of physical and behavioral factors, lean body mass and daily physical activity were associated with increased cycle variability and with the occurrence of long menstrual cycles, supporting the influence of these factors on estrogen-related processes and diseases. Peri- and post-menopausal fracture risk was significantly higher among women with a later age at menarche, longer mean cycle length, and longer bleeding duration during ages 28-32. 4)A population-based case-control study of 300 systemic lupus erythematosus patients is being developed to examine the role of endogenous and exogenous hormones, occupational exposure to silica and other dusts, infectious diseases, and genetic susceptibility in this endocrine-related autoimmune disorder.